title: Amyloid precursor proteins are constituents of the presynaptic active zone.
abstract: The amyloid precursor protein (APP) and its mammalian homologs, APLP1, APLP2, have been allocated to an organellar pool residing in the Golgi apparatus and in endosomal compartments, and in its mature form to a cell surface-localized pool. In the brain, all APPs are restricted to neurons; however, their precise localization at the plasma membrane remained enigmatic. Employing a variety of subcellular fractionation steps, we isolated two synaptic vesicle (SV) pools from rat and mouse brain, a pool consisting of synaptic vesicles only and a pool comprising SV docked to the presynaptic plasma membrane. Immunopurification of these two pools using a monoclonal antibody directed against the 12 membrane span synaptic vesicle protein2 (SV2) demonstrated unambiguously that APP, APLP1 and APLP2 are constituents of the active zone of murine brain but essentially absent from free synaptic vesicles. The specificity of immunodetection was confirmed by analyzing the respective knock-out animals. The fractionation experiments further revealed that APP is accumulated in the fraction containing docked synaptic vesicles. These data present novel insights into the subsynaptic localization of APPs and are a prerequisite for unraveling the physiological role of all mature APP proteins in synaptic physiology.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Goethe-University, Frankfurt am Main, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Laßek
authors.forename: Jens
authors.initials: J
authors.lastname: Weingarten
authors.forename: Ulf
authors.initials: U
authors.lastname: Einsfelder
authors.forename: Peter
authors.initials: P
authors.lastname: Brendel
authors.forename: Ulrike
authors.initials: U
authors.lastname: Müller
authors.forename: Walter
authors.initials: W
authors.lastname: Volknandt
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D005260:Female; D047468:Immunoprecipitation; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008854:Microscopy, Electron; D062105:Molecular Docking Simulation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000378:metabolism* / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000378:metabolism; D013569:Synapses / Q000648:ultrastructure
chemical_list: D016564:Amyloid beta-Protein Precursor; C498283:Aplp2 protein, rat; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D017661:Receptors, Presynaptic; C489618:Sv2a protein, rat
keywords: amyloid precursor proteins; docked synaptic vesicles; presynaptic active zone